2-Aryl-5-(perfluoroalkyl)pyrrole compounds are useful as insecticidal and acaricidal agents. In addition, those compounds are also useful for the preparation of other insecticidal and acaricidal agents. In particular, 2-aryl-5-(perfluoroalkyl)pyrrole compounds are key intermediates in the preparation of arylpyrrole compounds such as chlorfenapyr. Accordingly, there is an ongoing search to discover new methods for the preparation of 2-aryl-5-(perfluoroalkyl)pyrrole compounds.
U.S. Pat. No. 5,145,986 discloses that 2-aryl-5-(trifluoromethyl)pyrrole compounds may be prepared by reacting an N-(substituted benzyl)-2,2,2-trifluoroacetimidoyl chloride compound with an xcex1-halo-xcex1,xcex2-unsaturated nitrile, ester or nitro compound in the presence of a base. However, the process described in U.S. Pat. No. 5,145,986 is not entirely satisfactory because the required xcex1-halo-xcex1,xcex2-unsaturated nitrile, ester or nitro compound is prepared in a two stepxe2x80x94halogenation/dehydrohalogenationxe2x80x94process.
U.S. Pat. Nos. 5,446,170 and 5,426,225 disclose that 2-aryl-5-(trifluoromethyl)pyrrole compounds may be obtained in several steps from the appropriate aldehyde. The processes described in U.S. Pat. Nos. 5,446,170 and 5,426,225 require the use of an aminonitrile intermediate which is obtained via the Strecker synthesis from the appropriate aldehyde. However, the use of the Strecker synthesis is not entirely satisfactory because of cyanide containing waste streams.
It is, therefore, an object of the present invention to provide a new process for the preparation of 2-aryl-5-(perfluoroalkyl)pyrrole compounds which avoids the use of xcex1-halo-xcex1,xcex2-unsaturated nitrile, ester and nitro compounds and the Strecker synthesis.
It is also an object of this invention to provide a new process for the preparation of arylpyrrole compounds such as chlorfenapyr.
A further object of the present invention is to provide new intermediate compounds which are useful in the processes described hereinbelow.
Those and other objects of the present invention will become more apparent from the detailed description thereof set forth below.
The present invention provides a new process for the preparation of 2-aryl-5-(perfluoroalkyl)pyrrole compounds having the structural formula I 
wherein
W is hydrogen or CmF2m+1;
Y is CN, NO2 or CO2R;
R is C1-C4alkyl;
m and n are each independently an integer of 1, 2, 3, 4, 5, 6, 7 or 8;
A is 
L is hydrogen or halogen;
M and Q are each independently hydrogen, halogen, CN, NO2, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkylthio, C1-C4haloalkylthio, C1-C4-sulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C1-C4haloalkylsulfonyl or when M and Q are on adjacent positions they may be taken together with the carbon atoms to which they are attached to form a ring in which MQ represents the structure xe2x80x94OCH2Oxe2x80x94, xe2x80x94OCF2Oxe2x80x94 or xe2x80x94CHxe2x95x90CHxe2x80x94CHxe2x95x90CHxe2x80x94;
R1, R2 and R3 are each independently hydrogen, halogen, NO2, CHO or R2 and R3 may be taken together with the atoms to which they are attached to form a ring in which R2R3 is represented by the structure 
R4R5R6 and R7 are each independently hydrogen, halogen, CN or NO2; and
X is O or S
which process comprises reacting an N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compound having the structural formula II 
wherein A and n are as described above with a dieneophile compound having the structural formula III 
wherein W and Y are as described above and a base in the presence of a solvent.
The present invention further provides novel compounds having the structural formulas II, IV and V 
wherein n and A are as described hereinabove.
The process of the present invention preferably comprises reacting an N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compound of formula II with at least about one molar equivalent, preferably about one to four molar equivalents, of a dienophile compound of formula III and at least about one molar equivalent, preferably about one to four molar equivalents, of a base in the presence of a solvent preferably at a temperature range of about 5xc2x0 C. to 100xc2x0 C. to form 2-aryl-5-(perfluoroalkyl)pyrrole compounds of formula I.
Alternatively, the formula I compounds may be prepared by forming the formula III dienophile compounds in situ. This process comprises reacting an N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compound of formula II with preferably about one to four molar equivalents of a substituted haloethane compound having the structural formula VI 
wherein W and Y are as described hereinabove and Z is Cl, Br or I, and at least about two molar equivalents, preferably about two to five molar equivalents, of a base in the presence of a solvent preferably at a temperature range of about 5xc2x0 C. to 100xc2x0 C. to form 2-aryl-5-(perfluoroalkyl)pyrrole compounds of formula I.
Advantageously, the present invention provides new processes for the preparation of 2-aryl-5-(perfluoroalkyl)pyrrole compounds which avoid the use of xcex1-halo-xcex1,xcex2-unsaturated nitrile, ester and nitro compounds and the Strecker synthesis.
The formula I compounds of this invention may be isolated by conventional procedures such as dilution of the reaction mixture with water and filtration or, alternatively, extraction with a suitable solvent. Suitable extraction solvents include water-immiscible solvents such as ether, ethyl acetate, toluene, methylene chloride and the like.
Bases suitable for use in this invention include tri-(C1-C6alkyl)amines such as trimethylamine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine and the like; alkali metal carbonates such as potassium carbonate and sodium carbonate; alkali metal hydroxides such as potassium hydroxide and sodium hydroxide; alkali metal acetates such as potassium acetate and sodium acetate; and heterocyclic tertiary amines including, but not limited to, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU); 1,5-diazabicyclo[4.3.0]non-5-ene (DBN); 1,4-diazabicyclo[2.2.2]-octane; pyridine; substituted pyridines such as 2,6-dimethylpyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine and the like; quinoline; and substituted quinolines. Preferred bases include tri-(C1-C6alkyl)amines, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]-octane, potassium carbonate and sodium carbonate.
Solvents suitable for use in the present invention include, but are not limited to, carboxylic acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; N-substituted pyrrolidinones such as N-methylpyrrolidinone and the like; nitrites such as acetonitrile, propionitrile and the like; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride and the like; ethers such as tetrahydrofuran, dioxane and the like; sulfoxides such as dimethyl sulfoxide and the like; and mixtures thereof. Preferred solvents include carboxylic acid amides and nitrites and mixtures thereof. N,N-dimethylformamide and acetonitrile and mixtures thereof are especially preferred for use in the present invention.
Exemplary of halogen hereinabove are fluorine, chlorine, bromine and iodine. The terms xe2x80x9cC1-C4haloalkylxe2x80x9d, xe2x80x9cC1-C4haloalkoxyxe2x80x9d, xe2x80x9cC1-C4haloalkylthioxe2x80x9d, xe2x80x9c1-C1-C4haloalkylsulfinylxe2x80x9d and xe2x80x9cC1-C4haloalkylsulfonylxe2x80x9d are defined as a C1-C4alkyl, C1-C4alkoxy, C1-C4alkylthio, C1-C4alkylsulfinyl or C1-C4alkylsulfonyl group substituted with one or more halogen atoms, respectively.
The present invention is especially useful for the preparation of formula I compounds wherein
W is hydrogen;
Y is CN;
n is 1 or 2;
A is 
L is hydrogen or halogen; and
M and Q are each independently hydrogen, halogen, C1-C4haloalkyl or C1-C4haloalkoxy.
In particular, the present invention is useful for the preparation of
2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile;
2-(p-bromophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile;
2-(3,5-dichlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile;
2-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile; and
2-[4-(trifluoromethyl)phenyl]-5-(trifluoromethyl)pyrrole-3-carbonitrile, among others.
The present invention also relates to N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compounds having the structural formula II 
wherein
n is an integer of 1, 2, 3, 4, 5, 6, 7 or 8;
A is 
L is hydrogen or halogen;
M and Q are each independently hydrogen, halogen, CN, NO2, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkylthio, C1-C4haloalkylthio, C1-C4alkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C1-C4haloalkylsulfonyl or when M and Q are on adjacent positions they may be taken together with the carbon atoms to which they are attached to form a ring in which MQ represents the structure xe2x80x94OCH2Oxe2x80x94, xe2x80x94OCF2Oxe2x80x94 or xe2x80x94CHxe2x95x90CHxe2x80x94CHxe2x95x90CHxe2x80x94;
R1, R2 and R3 are each independently hydrogen, halogen, NO2, CHO or R2 and R3 may be taken together with the atoms to which they are attached to form a ring in which R2R3 is represented by the structure 
R4, R5, R6 and R7 are each independently hydrogen, halogen, CN or NO2; and
X is O or S.
Preferred formula II compounds of this invention are those wherein
n is 1 or 2;
A is 
L is hydrogen or halogen; and
M and Q are each independently halogen, C1-C4haloalkyl or C1-C4haloalkoxy.
Formula II compounds which are particularly useful in the processes of this invention include
N-[1-chloro-(2,2,2-trifluoroethyl)]-4-chlorobenzimidoyl chloride;
N-[1-chloro-(2,2,2-trifluoroethyl)]-4-bromobenzimidoyl chloride;
N-[1-chloro-(2,2,2-trifluoroethyl)]-3,5-dichlorobenzimidoyl chloride;
N-[1-chloro-(2,2,2-trifluoroethyl)]-3,4,5-trichlorobenzimidoyl chloride; and
N-[1-chloro-(2,2,2-trifluoroethyl)]-4-(trifluoromethyl)benzimidoyl chloride, among others.
Starting N-[1-chloro-1-(perfluoroalkyl)methyl]-arylimidoyl chloride compounds of formula II may be prepared, as shown in Flow Diagram I, by reacting an arylamide compound having the structural formula VII with a (perfluoroalkyl)aldehyde C1-C6alkyl hemiacetal compound having the structural formula VIII to form an N-[1-hydroxy-1-(perfluoroalkyl)methyl]arylamide compound having the structural formula IV, and reacting the formula IV compound with phosphorus pentachloride. 
Alternatively, N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compounds of formula II may be prepared, as shown in Flow Diagram II, by reacting an N-[1-hydroxy-1-(perfluoroalkyl)methyl]arylamide of formula IV with phosphorus trichloride to form an N-[1-chloro-1-(perfluoroalkyl)methyl]arylamide compound having the structural formula V, and reacting the formula V compound with phosphorus pentachloride. 
The present invention also relates to the formula IV and V compounds which are used to prepare the formula II compounds. In particular, the present invention provides N-[1-hydroxy-1-(perfluoroalkyl)methyl]arylamide compounds having the structural formula IV and N-[1-chloro-1-(perfluoroalkyl)methyl]arylamide compounds having the structural formula V 
wherein
n is an integer of 1, 2, 3, 4, 5, 6, 7 or 8;
A is 
L is hydrogen or halogen;
M and Q are each independently hydrogen, halogen, CN, NO2, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkylthio, C1-C4haloalkylthio, C1-C4alkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C1-C4haloalkylsulfonyl or when M and Q are on adjacent positions they may be taken together with the carbon atoms to which they are attached to form a ring in which MQ represents the structure xe2x80x94OCH2Oxe2x80x94, xe2x80x94OCF2Oxe2x80x94 or xe2x80x94CHxe2x95x90CHxe2x80x94CHxe2x95x90CHxe2x80x94;
R2, R2 and R3 are each independently hydrogen, halogen, NO2, CHO or R2 and R3 may be taken together with the atoms to which they are attached to form a ring in which R2R3 is represented by the structure 
R4, R5, R6 and R7 are each independently hydrogen, halogen, CN or NO2; and
X is O or S.
Preferred formula IV and V compounds of this invention are those wherein
n is 1 or 2;
A is 
L is hydrogen or halogen; and
M and Q are each independently halogen, C1-C4haloalkyl or C1-C4haloalkoxy.
Formula IV compounds which are particularly useful for the preparation of arylpyrrole compounds include
N-(1-hydroxy-2,2,2-trifluoroethyl)-4-chlorobenzamide;
N-(1-hydroxy-2,2,2-trifluoroethyl)-4-bromobenzamide;
N-(1-hydroxy-2,2,2-trifluoroethyl)-3,5-dichlorobenzamide;
N-(1-hydroxy-2,2,2-trifluoroethyl)-3,4,5-trichlorobenzamide; and
N-(1-hydroxy-2,2,2-trifluoroethyl)-4-(trifluoromethyl)benzamide, among others.
Formula V compounds which are particularly useful for the preparation of arylpyrrole compounds include
N-(1-chloro-2,2,2-trifluoroethyl)-4-chlorobenzamide;
N-(1-chloro-2,2,2-trifluoroethyl)-4-bromobenzamide;
N-(1-chloro-2,2,2-trifluoroethyl)-3,5-dichlorobenzamide;
N-(1-chloro-2,2,2-trifluoroethyl)-3,4,5-trichlorobenzamide; and
N-(1-chloro-2,2,2-trifluoroethyl)-4-(trifluoromethyl)benzamide, among others.
The formula I compounds are useful for the control of insect and acarid pests. In addition, the formula I compounds may be used to prepare other arylpyrrole insecticidal and acaricidal agents having the structural formula IX 
wherein
Y is CN, NO2 or CO2R;
R is C1-C4alkyl;
n is an integer of 1, 2, 3, 4, 5, 6, 7 or 8;
A is 
L is hydrogen or halogen;
M and Q are each independently hydrogen, halogen, CN, NO2, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkylthio, C1-C4haloalkylthio, C1-C4alkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C1-C4haloalkylsulfonyl or when M and Q are on adjacent positions they may be taken together with the carbon atoms to which they are attached to form a ring in which MQ represents the structurexe2x80x94OCH2Oxe2x80x94, xe2x80x94OCF2Oxe2x80x94 or xe2x80x94CHxe2x95x90CHxe2x80x94CHxe2x95x90CHxe2x80x94;
R1, R2 and R3 are each independently hydrogen, halogen, NO2, CHO or R2 and R3 may be taken together with the atoms to which they are attached to form a ring in which R2R3 is represented by the structure 
R4, R5, R6 and R7 are each independently hydrogen, halogen, CN or NO2;
X is O or S;
Hal is a halogen atom; and
J is hydrogen or C1-C6alkoxymethyl.
The present invention is especially useful for the preparation of arylpyrrole compounds of formula IX
wherein
Y is CN;
n is 1 or 2;
A is 
L is hydrogen or halogen;
M and Q are each independently hydrogen, halogen, C1-C4haloalkyl or C1-C4haloalkoxy;
Hal is Br or Cl; and
J is hydrogen or ethoxymethyl.
In particular, the present invention is useful for the preparation of formula IX arylpyrrole compounds such as
4-bromo-2-(p-chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile, (chlorfenapyr);
4-bromo-2-(3,5-dichlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile;
4-bromo-2-(3,5-dichlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile; and
4-bromo-2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile, among others.
Advantageously, formula IX arylpyrrole compounds may be prepared by a process which comprises:
(a) reacting an N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compound of formula II with a dienophile compound having the structural formula X 
xe2x80x83wherein Y is as described above and a base in the presence of a solvent to form a 2-aryl-5-(perfluoroalkyl)pyrrole compound having the structural formula XI 
(b) halogenating the formula XI compound to form the arylpyrrole compound of formula IX wherein J is hydrogen; and
(c) optionally alkoxymethylating the formula IX compound wherein J is hydrogen to form the formula IX arylpyrrole compound wherein J is C1-C6 alkoxymethyl.
Alternatively, arylpyrrole compounds of formula IX may be prepared by a process which comprises:
(a) reacting an N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compound of formula II with a substituted haloethane compound having the structural formula XII 
xe2x80x83wherein Y is as described above and Z is Cl, Br or I, and at least about two molar equivalents of a base in the presence of a solvent to form a 2-aryl-5-(perfluoroalkyl)pyrrole compound having the structural formula XI 
(b) halogenating the formula XI compound to form the arylpyrrole compound of formula IX wherein J is hydrogen; and
(c) optionally alkoxymethylating the formula IX compound wherein J is hydrogen to form the formula IX arylpyrrole compound wherein J is C1-C6alkoxymethyl.
Halogenation methods may be any known methods such as those described in U.S. Pat. Nos. 5,010,098 and 5,449,789.
Alkoxymethylation procedures suitable for use in this invention include conventional procedures known in the art (see, e.g., U.S. Pat. Nos. 5,010,098 and 5,359,090). In a preferred embodiment of this invention, the alkoxymethylation procedure comprises reacting a formula IX compound wherein J is hydrogen with a di-(C1-C6alkoxy)methane compound, N,N-dimethylformamide and phosphorous oxychloride in the presence of an aprotic solvent to form a reaction mixture and treating the reaction mixture with a tertiary amine.
In order to facilitate a further understanding of this invention, the following examples are presented primarily for the purpose of illustrating more specific details thereof. The scope of the invention should not be deemed limited by the examples, but encompasses the entire subject matter defined in the claims.